Accurate high-resolution and high-sensitivity mass measurements are important in many areas, such as for example proteomics and metabolomics. Fourier transform ion cyclotron resonance mass spectrometers (FTICR-MS) can provide high-performance mass measurements in part because such systems are capable of detecting ions for an extended period of time and of simultaneously detecting different ion species. Therefore, FTICR mass spectrometry has become an important analytical tool for ion analysis and especially in the analysis of complex mixtures.
A FTICR-MS is a type of mass analyzer (i.e., mass spectrometer) for determining a mass-to-charge ratio (m/z) of ions based on a measured frequency of ion motion in a magnetic field. In a basic implementation of a FTICR-MS, gaseous ions are accumulated and introduced into a detection element of a FTICR-MS instrument, such as an ion-cyclotron resonance (ICR) cell or an ion-trapping cell, situated within a strong magnetic field. The magnetic field is typically aligned along a z-axis or a central longitudinal axis of the cell. The cell includes trapping electrodes that produce an electric field to trap ions within the cell along the z-axis. The trapped ions typically have non-zero kinetic energies in the z-direction and move along the z-axis of the cell following spring-like paths, wherein the spring-like paths are compressed near the longitudinal termini of the cell.
Trapped ions are induced into orbital motion about the z-axis or in an x-y plane of the ICR cell as a result of the Lorentz force and the interaction of ions with electric and magnetic fields in the cell. The net motion of the ions in the cell is a combination of longitudinal travel along the z-axis and latitudinal orbital motion about the z-axis. An orbital component of an ion's motion can be referred to as “cyclotron motion.” The periodicity of this cyclotron motion, referred to as the “cyclotron frequency,” is related to the m/z of the ion. Typically, an RF (radio frequency) voltage is applied to excitation electrodes to produce an oscillating electric field that induces resonant excitation of the orbiting ions. Ions of the same m/z are excited together and form a coherent ion cloud or ion packet having increased spatial coherence. Resonant excitation also transfers kinetic energy to the ions, thereby increasing their cyclotron orbital radii about the z-axis. The excitation electric field can therefore be used to improve ion detection through formation of ion packets having measurable respective cyclotron frequencies.
As ion packets traverse their cyclotron orbits, they induce oscillating currents in detection electrodes. The detected oscillatory signal is representative of an image current produced as a packet of ions passes close to detection electrodes while orbiting about the z-axis. Accordingly, the relative distance of the packet from the detection electrodes and the collective charge of ions in the packet are directly related to intensity of the detected signal. Typically, a free induction decay (FID) or time-domain signal is measured. The FID signal is an interferogram or a superposition of sine waves representing ions of different m/z values orbiting in the ICR cell. The waves decay in amplitude over time as the radius and/or phase coherence of the orbital motion of the ions decreases. Since the m/z of an ion is inversely proportional to the cyclotron frequency of the ion, a mass spectrum can be extracted from the FID signal by Fourier transforming the signal to generate a frequency spectrum. The frequency spectrum can be converted to a mass spectrum using a calibration equation relating frequency to m/z.
Resolution, mass accuracy, and sensitivity of FTICR-MS measurements can be improved by increasing the length of the time-domain signal, increasing the radius of ion motion, or increasing the detectable duration of an FID signal. But, FID-signal duration can be disadvantageously decreased by events such as ion collisions and ion de-phasing. Ion collisions generate what is known in the art as coalitional damping, which is a decrease in the ion's cyclotron radius due to a loss of kinetic energy through collisions of the ion with other ions, molecules, or atoms in the ICR cell. Ion de-phasing occurs when an ion cloud loses phase coherence. For example, ions with the same m/z can become distributed at varying cyclotron phase angles rather than remaining in a coherent ion packet. Ion de-phasing also reduces the magnitude of a detected signal. A number of different processes have been identified as contributing to de-phasing of ion clouds. For example, ion-cloud density, magnetic field strength, Coulombic interactions with other ion clouds, total cloud charge, magnetron motion, and ion velocity can have respective effects on de-phasing. Ion packets may become more stable as the number of charges in the ion packets increase, and such increased ion-cloud stability may reduce de-phasing.
Therefore, there is a need in the art for methods and apparatus that can improve performance of FTICR mass spectrometry systems through the minimization of the effects that lead to ion collisions and ion de-phasing.